Emerging treatments for choroidal metastases

Abstract

It has been over a century since Perls described the first case of choroidal metastasis. For the next six decades only 230 cases were described in the literature. Today, however, ocular metastasis is recognized as the most common intraocular malignancy. Thanks to recent advances in treatment options for metastatic disease, patients are living longer, and choroidal metastases will become an increasingly important issue for oncologists and ophthalmologists alike. We summarize the current knowledge of choroidal metastases and examine their emerging systemic and local therapies. Targeted therapies for metastatic lung, breast, and colon cancer--the most common causes of choroidal metastases--are reviewed in detail with the goal of identifying the most effective treatment strategies.

Fig. 1

A: Initial presentation of a choroidal metastasis with orange, leopard-spotted lesion that was associated with subretinal fluid. B: Initial echographic appearance of a dome-shaped lesion with irregular reflectivity, and a maximal elevation of 2.9 mm. C: Choroidal metastasis after response from systemic therapy. D: Echography shows reduction in thickness to 1.0 mm. E: Choroidal metastases appears as a flat scar. F: Echography shows minimal thickening (<1.0 mm).

Fig. 2

A: The EGFR-dependent signaling pathway. The receptor-specific ligand binds to the extracellular domain of the single-chain EGFR or EGFR-related receptors such as HER2. Then, the ligand-bound EGFR forms activated homodimers or heterodimers leading to ATP-dependent phosphorylation of specific tyrosine residues on the in-tracellular domain. This phosphorylation triggers downstream signaling to the cytoplasm and then nucleus. The two major pathways activated by EGFR are (1) the RAS-RAF-MEK-MAPK pathway that regulates gene transcription, cell-cycle progression from the G1 to the S phase, and cell proliferation, and (2) the PI3K-Akt pathway that activates a cascade of anti-apoptotic and prosurvival signals. B: Monoclonal antibodies bind to the extracellular domain of EGFR or EGFR-like receptor and block ligand binding, receptor activation, and downstream signaling. C: Tyrosine kinase inhibitors compete with ATP binding sites on the intracellular tyrosine kinase catalytic domain blocking phosphorylation and subsequent downstream effects. mAb = monoclonal antibody; EGFR = epidermal growth factor receptor; HER2 =human epidermal growth factor receptor 2; MAPK = mitogen-activated protein kinase; VEGF = vascular endothelial growth factor; PI3K = phosphatidylinositol 3,45-kinase.